1a: Finding the causes of major depression is a major challenge in global health. One critical question is the extent to which our current classification conceals within the diagnosis of major depressive disorder multiple conditions, each the outcome of different causal pathways. For example there is evidence that the genetic loci that increase risk for depression differ between men and women. We wish to use the phenotypes in Biobank to address whether depression is one condition or many.

1b: Depression is the leading cause of morbidity in the developed world and predicted to become the world’s leading cause of morbidity by 2030. It is also a common cause of death: 800,000 people kill themselves every year, and the majority do so in part because they are depressed. Our project to find causes of depression is addressing a global health problem

1c: We will classify depression into subtypes, using known or putative causes of heterogeneity, such as age, sex and severity of illness. We will then examine whether the genetic effects on different types of depression are the same. In order to test for clinical heterogeneity we will apply tests that use differences in the way genetic loci act to detect different categories of disease